1. Field of the Invention
The present invention generally relates to anti-transferrin receptor antibodies and their use in the treatment of cancer.
2. Description of the Related Art
Multiple myeloma is a clonal B-cell malignancy that accounts for 10-15% of hematopoietic malignancies and 2% of all cancer deaths in the United States. See Jemal et al. (2010) CA Cancer J Clin 60(5):277-300. Within the past decade the overall survival rate of multiple myeloma has increased dramatically due to the utilization of thalidomide and its derivative lenalidomide, as well as the proteosome inhibitor bortezomib. See Laubach et al. (2010) Med Oncol 27(Suppl 1):S1-S6. Combination therapies of these new drugs with dexamethasone, prednisone, melphalan, or anthracyclines (with or without autologous stem cell transplantation) have improved survival of multiple myeloma patients. See Palumbo et al. (2009) Leukemia 23(3):449-56. However, multiple myeloma remains incurable and novel therapies are still needed. Additionally, there are no FDA-approved antibody-based therapies for the treatment of multiple myeloma. A successful antibody-based therapy for other B-cell malignancies is rituximab (Rituxan®), a chimeric IgG1 that targets CD20. See Bello & Sotomayor (2007) Hematology Am Soc Hematol Educ Program 233-242. This antibody alone or combined with various forms of chemotherapy is FDA approved for the treatment of B-cell malignancies including chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). Due to the small percentage of multiple myeloma that are CD20+ (13-22%), rituximab is not a common treatment for multiple myeloma. Additionally, only 10% of CD20+ multiple myeloma patients have shown a partial response to rituximab treatment. See Kapoor et al. (2008) Br J Haematol 141(2):135-148. In lymphoma patients where rituximab has significantly increased survival, resistance to treatment continues to be a problem. See Oflazoglu & Audoly (2010) mAbs 2(1):14-19. Therefore, there is still a need for the development of new therapies for the treatment of B-cell malignancies as a whole, and for multiple myeloma in particular.